Phosphorylation of G Protein–Coupled Receptors: GPCR Kinases in Heart Disease

Domain structure of the GPCR kinases (GRKs). The central catalytic domain that typifies GRKs is similar to catalytic sequences from other serine/threonine kinases. The N- and C-terminal domains appear to determine the specific interactions between any given GRK and other proteins and components of the cell membrane. Of particular note is the C-terminal domain, which governs interaction with the Gβγheterodimer released upon activation G proteins. The C-terminal domain of βARK1 (i.e., of GRK2), denoted here as βARKct, has been transgenically expressed with therapeutic efficacy in a variety of cardiomyopathic models. See text for details.